It is sometimes desirable to deliver (e.g., inject, infuse, apply, etc) two or more chemical substances to a desired location within the body of a human or animal subject such that the substances become combined or mixed shortly before, during or shortly after delivery into the body. For example, some therapies involve the administration of two or more component substances (e.g., chemical compounds, solutions, suspensions, biologics, cells, reactants, etc.) such that those substances react or otherwise interact with each other to form a resultant mixture or reaction product that directly or indirectly results in some therapeutic, diagnostic or cosmetic benefit (generally referred to herein as “Multiple-Component Therapies”). In some cases, it is important for the component substances to be combined or mixed immediately before, during or after delivery. This is the case, for example, when mixing or combining of the component substances too long before delivery would result in an increase in viscosity or solidification process that would render the product incapable of passing through an intended delivery cannula or needle or where the product has a very short half life and would loose activity before reaching its intended in vivo destination.
One Multiple Component Therapy is known as platelet gel (PG). In this therapy, a platelet-containing component (e.g., platelet rich plasma (PRP)) is combined with a thrombin-containing component (e.g, a thrombin solution) immediately before, during or after injection into the myocardium at one or more location(s) within or near an infarct or other myocardial injury. The platelet-containing component (e.g., PRP) combines with the thrombin-containing component and forms a platelet gel (PG) which causes the desired therapeutic effect. Such PG is formed when components (such as fibrinogen) contained in the platelet-containing component are activated by thrombin contained in the thrombin-containing component. Autologous PRP can be obtained from the subject's own blood, thereby significantly reducing the risk of adverse reactions or infection. When autologous PRP is used as the platelet-containing component, the resultant PG is referred to as autologous platelet gel (APG). The addition of thrombin to platelet-containing plasma products such as PRP is described in detail in U.S. Pat. No. 6,444,228, the disclosure of which is expressly incorporated herein by reference. PRP has also been used in a variety of orthopedic and other applications.
Moreover, the preparation and use of PG and APG for improving cardiac function and/or preventing deleterious ventricular remodeling following myocardial infarction or other injury to the myocardium is being investigated by Medtronic Vascular, Inc. of Santa Rosa, Calif., as described in parent U.S. patent application Ser. No. 11/426,219 (published as 2007-0014784) and in United States Patent Application Publication Nos. 2006/0041242 and 2005/209564, the entire disclosures of which are expressly incorporated herein by reference. Since it may be difficult to pass PG or APG through the lumen of a needle, it is desirable to inject the platelet-containing component and the thrombin-containing component such that they become mixed immediately prior to, during or after injection through the needle. Additionally, injecting the platelet-containing component and the thrombin-containing component separately or immediately after mixing may allow the infusate to distribute to a greater area before fully gelling into the PG or APG, thereby possibly enhancing the effect of this therapy.
Other examples of Multiple Component Therapies known in the prior art include, but are not limited to; multiple component tissue adhesives and sealants (e.g., Tisseel VH™ Fibrin Sealant, available commercially from Baxter Healthcare Corporation, Deerfield, Ill.); tissue bulking agents, fillers or polymeric materials (e.g., hydrogels) that may be formed or expanded in situ for various therapeutic or cosmetic applications such as tissue bulking, filling or expanding and various prodrug+activator combinations.
The prior art has also included a number of injector assemblies that may be usable for delivering Multiple Component Therapies. For example, U.S. Pat. No. 4,823,985 (Grollier, et al.) describes a dispensing assembly usable for dispensing at least two constituents such that the constituents become mixed to form a homogenous product. This dispensing assembly has flexible walls and at least two compartments, including outlet orifices located adjacent to one another so that when the outlet orifices are opened as by cutting, and pressure is applied to the flexible walls, dispensing and immediate mixing of the constituents will be effected; the viscosity and volumes of the constituents are selected to have certain values to enable the dispensing to properly mix the constituents to form a homogenous product. The dispensing assemblies described in U.S. Pat. No. 4,823,985 (Grollier et al.) do not include any needle having a tissue penetrating tip or other means for injecting the constituents into tissue.
U.S. Pat. No. 6,936,033 (McIntosh, et al.) describes a double syringe system for holding a pair of syringes in a manner so as to accommodate the simultaneous activation of the plunger of each syringe in order to effect simultaneous delivery of the contents of each syringe. The delivery system includes a support member that is positioned between the two syringe bodies. The elongated support member has resilient, C-shaped clamps on one end of the support member. The clamps are designed to be removably clamped onto the applicator so that the syringe barrels will be held together in a parallel manner. The elongated support member further comprises finger grips. A plunger connects the two syringe plungers so that they can also be simultaneously activated. Two side-by-side cannulas extend from the distal end of the delivery system and, as the plungers are depressed, the material from one syringe flows through one cannula and the material from the other syringe flows through the other cannula. The distal ends of the cannulas are aligned with each other so that there will be simultaneous delivery of the separated fluids from both syringes to the application site. In one embodiment, the side-by-side cannulas comprise needles of substantially equal length. Each of these needles bent towards each other so that as the needles approach their distal ends, they run parallel to each other and touch. The parallel portions of needles can be joined together with a sleeve, adhesive, or other methods known in the art. In another embodiment, the cannulas are formed of flexible lengths of tubing that are cut off at equivalent lengths and attached at their distal ends, usually with solvent adhesive. In yet another embodiment, the delivery system has a delivery tip that comprises a hollowed double fluid path attached to a single cannula fitting such as that described in U.S. Pat. No. 5,104,375, which is specifically incorporated herein by reference. Alternatively, the delivery system may have spray heads attached to each syringe.
U.S. Pat. No. 6,942,639 (Baugh et al.) describes a system for delivering and combining an activated blood component and an inactivated blood component, which combine to form APG. This system comprises separate chambers which contain the activated blood component and the inactivated blood component, respectively. The first chamber includes an activating agent and a filter (which may be one and the same) which causes a clot (which forms in the blood component) to become triturated, thereby isolating thrombin from the clot. The second chamber stores the inactivated blood component (e.g., PRP) that, when mixed with thrombin, produces a gel. The first or second chamber may further contain agents which are desired to be delivered to a specific site. The design of the delivery system allows for ease in operation of combining two agents at a specific time and place.
United States Published Patent Application 2006/0253082 describes dispensing systems and methods for dispensing platelet gel or other two component treatments. These dispensing systems include a handle assembly that is designed to hold two syringes and thumb plate that is used to depress the plungers of both syringes simultaneously. The fluids contained in the separate syringes then flow through separate channels in a manifold and through a tip assembly. In various embodiments the tip assembly may include specialized various nozzles that entrain non-atomized flow of a first fluid in an atomized flow of a second fluid, delivering a first fluid upstream from a second fluid, delivering a first fluid and a second fluid with re-shapeable malleable tubes, delivering first and second fluids with releasable connectors maintained by a handle assembly.
There remains a need for the development of new devices and methods for injecting platelet gel or other Multiple Component Therapies to selected locations within the bodies of human or animal subjects such that the component substances become mixed or combined immediately before, during or after delivery into or onto the body of the subject.